Fig. 1: Increased endogenous GDNF levels increase striatal dopamine function. See also Supplementary Fig. S1. | Molecular Psychiatry

Fig. 1: Increased endogenous GDNF levels increase striatal dopamine function. See also Supplementary Fig. S1.

From: Elevated endogenous GDNF induces altered dopamine signalling in mice and correlates with clinical severity in schizophrenia

Fig. 1

A Schematic of the Gdnf cHyper allele (top panel) and the resulting mRNA carrying a short 3'UTR (bottom panel) devoid of negative regulation elements in the 3'UTR. pA, polyadenylation signal. B Schematic of the conditional gene upregulation strategy to elevate endogenous gene expression in natively expressing cells. When using the conditional hypermorph allele, Cre-mediated recombination would result in an elevated gene expression specifically in cells that normally express the gene. C Striatal Gdnf mRNA levels in adult Gdnf cHyper;Nestin-Cre mice, measured with qPCR. Box plots show median, upper, and lower quartiles, as well as maximum and minimum values. N = 7–17 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. ***p < 0.001. D Total tissue dopamine levels in the striatum, measured with HPLC. Box plots show median, upper, and lower quartiles, as well as maximum and minimum values. N = 4–10 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. *p < 0.05. E Total tissue dopamine levels in the substantia nigra, measured with HPLC. Box plots show median, upper, and lower quartiles, as well as maximum and minimum values. N = 5–10 mice per group. One-way ANOVA, Tukey’s multiple comparisons test. *p < 0.05. F Gdnf mRNA expression pattern in dorsal striatum, detected using RNAscope probes. Arrows indicate cells with high Gdnf signal. Scale bar 50 µm (d, left panels) or 10 µm (d, right panels, higher magnification). G Stimulated dopamine release in striatal slices across four consecutive stimulations, measured with fast-scan cyclic voltammetry. Mean ± SEM. n = 10–20 striatal slices (from N = 4–8 mice) per group. Two-way repeated measures ANOVA, Tukey’s multiple comparisons test. *p < 0.05; **p < 0.01 between cHyper/cHyper +Cre and wt/wt +Cre. H Similar to (G) but showing dopamine re-uptake. Mean ± SEM. n = 10–20 striatal slices (from N = 4–8 mice) per group. Two-way repeated measures ANOVA, Tukey’s multiple comparisons test. #p < 0.05 between wt/cHyper +Cre and wt/wt +Cre.

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